Variant X-70277417-G-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Likely benign. Variant got -4 ACMG points: 0P and 4B. BS2

The NM_004312.3(ARR3):c.497G>A(p.Arg166Gln) variant causes a missense change. The variant allele was found at a frequency of 0.0000232 in 1,209,491 control chromosomes in the GnomAD database, with no homozygous occurrence. There are 8 hemizygotes in GnomAD. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.000080 ( 0 hom., 1 hem., cov: 23)

Exomes 𝑓: 0.000017 ( 0 hom. 7 hem. )

Consequence

ARR3
NM_004312.3 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 4.29

Variant links:

Genes affected

ARR3 (HGNC:710): (arrestin 3) The protein encoded by this gene is a non-visual arrestin which binds to agonist-activated, phosphorylated G protein-coupled receptors. This binding uncouples the receptor from the heterotrimeric G protein, resulting in termination of the G protein-coupled receptor signaling. The encoded protein also is a part of the centrosome, interacting with gamma-tubulin to help regulate proper centrosome function. [provided by RefSeq, May 2016]

ARR3 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -4 ACMG points.

BS2

High Hemizygotes in GnomAdExome4 at 7 XL gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ARR3	NM_004312.3 link	c.497G>A	p.Arg166Gln	missense_variant	Exon 9 of 17	ENST00000307959.9	NP_004303.2	P36575-1
ARR3	XM_047442105.1 link	c.521G>A	p.Arg174Gln	missense_variant	Exon 8 of 16		XP_047298061.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ARR3	ENST00000307959.9 link	c.497G>A	p.Arg166Gln	missense_variant	Exon 9 of 17	1	NM_004312.3	ENSP00000311538.8		P36575-1
ARR3	ENST00000374495.7 link	c.497G>A	p.Arg166Gln	missense_variant	Exon 9 of 16	1		ENSP00000363619.3		P36575-2

Frequencies

GnomAD3 genomes

AF:

0.0000804

AC:

AN:

111879

Hom.:

Cov.:

AF XY:

0.0000293

AC XY:

AN XY:

34081

show subpopulations

Gnomad AFR

AF:

0.000163

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000189

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000377

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.0000386

AC:

AN:

181421

Hom.:

AF XY:

0.0000303

AC XY:

AN XY:

65989

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.000147

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000370

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000173

AC:

AN:

1097612

Hom.:

Cov.:

AF XY:

0.0000193

AC XY:

AN XY:

363004

show subpopulations

Gnomad4 AFR exome

AF:

0.0000379

Gnomad4 AMR exome

AF:

0.000142

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.0000119

Gnomad4 OTH exome

AF:

0.0000651

GnomAD4 genome

AF:

0.0000804

AC:

AN:

111879

Hom.:

Cov.:

AF XY:

0.0000293

AC XY:

AN XY:

34081

show subpopulations

Gnomad4 AFR

AF:

0.000163

Gnomad4 AMR

AF:

0.000189

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.0000377

Gnomad4 OTH

AF:

0.00

Alfa

AF:

0.0000868

Hom.:

Bravo

AF:

0.0000642

ESP6500AA

AF:

0.00

AC:

ESP6500EA

AF:

0.000149

AC:

ExAC

AF:

0.0000412

AC:

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

Inborn genetic diseases

Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Dec 18, 2023

The c.497G>A (p.R166Q) alteration is located in exon 9 (coding exon 8) of the ARR3 gene. This alteration results from a G to A substitution at nucleotide position 497, causing the arginine (R) at amino acid position 166 to be replaced by a glutamine (Q). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Uncertain

0.37

BayesDel_addAF

Benign

-0.40

BayesDel_noAF

Benign

-0.55

CADD

Benign

DANN

Pathogenic

1.0

DEOGEN2

Benign

0.36

.;.;T

FATHMM_MKL

Uncertain

0.94

LIST_S2

Uncertain

0.96

D;D;D

M_CAP

Benign

0.044

MetaRNN

Uncertain

0.66

D;D;D

MetaSVM

Benign

-0.67

MutationAssessor

Pathogenic

3.3

M;.;M

PrimateAI

Benign

0.36

PROVEAN

Uncertain

-4.0

D;.;D

REVEL

Benign

0.25

Sift

Uncertain

0.0010

D;.;D

Sift4G

Uncertain

0.033

D;D;D

Polyphen

1.0

D;.;D

Vest4

0.70

MVP

0.33

MPC

0.46

ClinPred

0.82

GERP RS

1.9

Varity_R

0.71

gMVP

0.72

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.010

Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over